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Monkeypox virus (MPV) infection has developed into a re-emerging disease, and despite the potential of tecovirimat and cidofovir drugs, there is currently no conclusive treatment. The treatment's effectiveness and cost challenges motivate us to use In Silico approaches to seek natural compounds as candidate antiviral inhibitors. Using Maestro 11.5 in Schrodinger suite 2018, available natural molecules with validated chemical structures collected from Eximed Laboratory were subjected to molecular docking and ADMET analysis against the highly conserved A42R Profilin-like Protein of Monkeypox Virus Zaire-96-I-16 (PDB: 4QWO) with resolution of 1.52 Å solved 3D structure. Compared to the FDA-approved Tecovirimat, molecular docking revealed that Salsoline derivatives, Genistein, Semisynthetic derivative of kojic acid, and Naringenin had strengthened affinity (-8.9 to -10 kcal/mol) to 4QWO, and the molecular dynamic's simulation confirmed their high binding stability. In support of these results, the hydrogen bond analysis indicated that the Salsoline derivative had the most robust interaction with the binding pockets of 4QWO among the four molecules. Moreover, the comparative free energy analyses using MM-PBSA revealed an average binding free energy of the complexes of Salsoline derivative, Genistein, Semisynthetic derivative of kojic acid, Naringenin, of -106.418, -46.808, -50.770, and -63.319 kJ/mol, respectively which are lower than -33.855 kJ/mol of the Tecovirimat complex. Interestingly, these results and the ADMET predictions suggest that the four compounds are promising inhibitors of 4QWO, which agrees with previous results showing their antiviral activities against other viruses., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chebaibi, Bourhia, Amrati, Slighoua, Mssillou, Aboul-Soud, Khalid, Hassani, Bousta, Achour, Benhida and Daoud.)

This work investigated elemental sulfur (S 0 ) biorecovery from Phosphogypsum (PG) using sulfur-oxidizing bacteria in an O 2 -based membrane biofilm reactor (MBfR). The system was first optimized using synthetic sulfide medium (SSM) as influent, then switched to biogenic sulfide medium (BSM) generated by biological reduction of PG alkaline leachate. The results using SSM had high sulfide-oxidation efficiency (98 %), sulfide to S 0 conversion (∼90 %), and S 0 production rate up to 2.7 g S 0 /(m 2 .d), when the O 2 /S ratio was ∼0.5 g O 2 /g S. With the BSM influent, the system maintained high sulfide-to-S 0 conversion rate (97 %), and S 0 -production rate of 1.6 g S 0 /(m 2 .d). Metagenomic analysis revealed that Thauera was the dominant genus in SSM and BSM biofilms. Furthermore, influent composition affected the bacterial community structure and abundances of functional microbial sulfur genes, modifying the sulfur-transformation pathways in the biofilms. Overall, this work shows promise for O 2 -MBfR usage in S 0 biorecovery from PG-leachate and other sulfidogenic effluents., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Karim Lyamlouli reports financial support was provided by OCP Group. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

CXCR1/2 biomolecules play vital roles in cancer cell proliferation, tumor inflammation, and angiogenesis, making them attractive drug targets. In clear cell renal cell carcinoma (RCC) and head and neck squamous cell carcinoma (HNSCC), where CXCR1/2 is overexpressed, inhibition studies are limited. Building upon previous research efforts, we investigated new N , N '-diarylurea analogues as ELR + CXCL-CXCR1/2 inhibitors. Evaluations on RCC and HNSCC cell lines and 3D spheroid cultures identified compound 10 as a lead molecule, exhibiting significant inhibition of invasion, migration, and neo-angiogenesis. It demonstrated strong interference with the signaling pathway, with high selectivity toward kinases. In vivo studies on zebrafish embryos and RCC xenografted mice showed notable anticancer, antimetastatic, and antiangiogenic effects after oral administration and minimal toxicity. Compound 10 emerges as a promising candidate for further preclinical development as an oral anticancer and antiangiogenic drug targeting the ELR + CXCL-CXCR1/2 pathway., Competing Interests: The authors declare the following competing financial interest(s): L.C.P.G. reports financial support was provided by Roca Therapeutics. O.R. reports financial support was provided by Roca Therapeutics. J.L.D. reports financial support was provided by Roca Therapeutics. M.D. reports a relationship with Roca Therapeutics that includes: board membership. G.P. reports a relationship with Roca Therapeutics that includes: board membership. R.B. reports a relationship with Roca Therapeutics that includes: board membership. C.R. reports a relationship with Roca Therapeutics that includes: board membership. M.D. has Patent WO2020079184A2 licensed to Roca Therapeutics. G.P. has Patent WO2020079184A2 pending to Roca Therapeutics. R.B. has Patent WO2020079184A2 licensed to Roca Therapeutics. C.R. has Patent WO2020079184A2 licensed to Roca Therapeutics. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 American Chemical Society.)

Background: In clear cell renal cell carcinoma (ccRCC), first-line treatment combines nivolumab (anti-PD-1) and ipilimumab (anti-CTLA4), yielding long-term remissions but with only a 40% success rate. Our study explored the potential of enhancing ccRCC treatment by concurrently using CXCR2 inhibitors alongside immunotherapies., Methods: We analyzed ELR + CXCL levels and their correlation with patient survival during immunotherapy. RCT001, a unique CXCR2 inhibitor, was examined for its mechanism of action, particularly its effects on human primary macrophages. We tested the synergistic impact of RCT001 in combination with immunotherapies in both mouse models of ccRCC and human ccRCC in the presence of human PBMC., Resuts: Elevated ELR + CXCL cytokine levels were found to correlate with reduced overall survival during immunotherapy. RCT001, our optimized compound, acted as an inverse agonist, effectively inhibiting angiogenesis and reducing viability of primary ccRCC cells. It redirected M2-like macrophages without affecting M1-like macrophage polarization directed against the tumor. In mouse models, RCT001 enhanced the efficacy of anti-CTLA4 + anti-PD1 by inhibiting tumor-associated M2 macrophages and tumor-associated neutrophils. It also impacted the activation of CD4 T lymphocytes, reducing immune-tolerant lymphocytes while increasing activated natural killer and dendritic cells. Similar effectiveness was observed in human RCC tumors when RCT001 was combined with anti-PD-1 treatment., Conclusions: RCT001, by inhibiting CXCR2 through its unique mechanism, effectively suppresses ccRCC cell proliferation, angiogenesis, and M2 macrophage polarization. This optimization potentiates the efficacy of immunotherapy and holds promise for significantly improving the survival prospects of metastatic ccRCC patients., (© 2024. The Author(s).)